Identification of a novel cancer microbiome signature for predicting prognosis of human breast cancer patients

BackgroundPrognosis of breast cancer (BC) patients differs considerably and identifying reliable prognostic biomarker(s) is imperative. With evidence that the microbiome plays a critical role in the response to cancer therapies, we aimed to identify a cancer microbiome signature for predicting the prognosis of BC patients.MethodsThe TCGA BC microbiome data (TCGA-BRCA-microbiome) was downloaded from cBioPortal. Univariate and multivariate Cox regression analyses were used to examine association of microbial abundance with overall survival (OS) and to identify a microbial signature for creating a prognostic scoring model. The performance of the scoring model was assessed by the area under the ROC curve (AUC). Nomograms using the microbial signature, clinical factors, and molecular subtypes were established to predict OS and progression-free survival (PFS).ResultsAmong 1406 genera, the abundances of 94 genera were significantly associated with BC patient OS in TCGA-BRCA-microbiome dataset. From that set we identified a 15-microbe prognostic signature and developed a 15-microbial abundance prognostic scoring (MAPS) model. Patients in low-risk group significantly prolong OS and PFS as compared to those in high-risk group. The time-dependent ROC curves with MAPS showed good predictive efficacy both in OS and PFS. Moreover, MAPS is an independent prognostic factor for OS and PFS over clinical factors and PAM50-based molecular subtypes and superior to the previously published 12-gene signature. The integration of MAPS into nomograms significantly improved prognosis prediction.ConclusionMAPS was successfully established to have independent prognostic value, and our study provides a new avenue for developing prognostic biomarkers by microbiome profiling.

Identification of a novel cancer microbiome signature for predicting prognosis of human breast cancer patients.

BACKGROUND: Prognosis of breast cancer (BC) patients differs considerably and identifying reliable prognostic biomarker(s) is imperative. With evidence that the microbiome plays a critical role in the response to cancer therapies, we aimed to identify a cancer microbiome signature for predicting the prognosis of BC patients. METHODS: The TCGA BC microbiome data (TCGA-BRCA-microbiome) was downloaded from cBioPortal. Univariate and multivariate Cox regression analyses were used to examine association of microbial abundance with overall survival (OS) and to identify a microbial signature for creating a prognostic scoring model. The performance of the scoring model was assessed by the area under the ROC curve (AUC). Nomograms using the microbial signature, clinical factors, and molecular subtypes were established to predict OS and progression-free survival (PFS). RESULTS: Among 1406 genera, the abundances of 94 genera were significantly associated with BC patient OS in TCGA-BRCA-microbiome dataset. From that set we identified a 15-microbe prognostic signature and developed a 15-microbial abundance prognostic scoring (MAPS) model. Patients in low-risk group significantly prolong OS and PFS as compared to those in high-risk group. The time-dependent ROC curves with MAPS showed good predictive efficacy both in OS and PFS. Moreover, MAPS is an independent prognostic factor for OS and PFS over clinical factors and PAM50-based molecular subtypes and superior to the previously published 12-gene signature. The integration of MAPS into nomograms significantly improved prognosis prediction. CONCLUSION: MAPS was successfully established to have independent prognostic value, and our study provides a new avenue for developing prognostic biomarkers by microbiome profiling.

Factors associated with overall survival and relief of dysphagia in advanced esophageal cancer patients after 125I seed-loaded stent placement: a multicenter retrospective analysis.

Iodine-125 (125I) seed-loaded stent placement has served as an effective palliation for malignant esophageal strictures in China. We performed a retrospective study to identify the prognostic factors of this irradiation stent placement in advanced esophageal cancer patients. A total of 201 patients who underwent 125I seed-loaded stent placement were included in this study from June 2012 to March 2016 at five hospitals in China. The Cox regression models adjusted for stratification factors were used, and a stepwise multivariate analysis was performed to predict the overall survival and relief of dysphagia on the basis of pretreatment clinical characteristics, respectively. Three independent prognostic factors were identified for overall survival: histopathological subtype (squamous cell carcinoma vs. adenocarcinoma, hazard ratio [HR] 1.45, 95% confidence interval [CI95%]: 1.01-2.09, P = 0.046), serum total protein (≥66 g/L vs. <66 g/L, HR 0.61, CI95%: 0.48-0.59, P = 0.023), and performance status (<2 vs. ≥2, HR 1.57, CI95%: 1.09-2.08, P = 0.013). Four factors were significantly associated with the relief of dysphagia: T stage (T3 vs. T4, P = 0.003), tumor location (superior vs. inferior, P = 0.049), tumor-node-metastasis classification (IV vs. II, P = 0.025), and age (≥71 years vs. <71 years, P = 0.029). Prognostic factors identified from this analysis can be used to aid clinical decision-making and design future clinical trials.

[Preliminavy clinical study of the treatment of hemorrhoids by superselective embolization of superior rectal artery].

Objective: To investigate the safety and feasibility of the treatment of hemorrhoids by superselective arterial embolization. Methods: The clinical data of 15 patients with grade Ⅱ to Ⅳ hemorrhoids were collected who were treated by superselective SRA embolization.According to the number and shape of SRA in the vicinity of the dentate line, chosed coils, PVA particles and gelfoam particles, ethanol and bletilla mixture of gelfoam particles for embolization.And intraoperative operations, postoperative complications, follow-up treatment results were observed. Results: The interventional procedures were successfully accomplished in all 15 cases.The operation time was (30±14) min, and the hospital stay was 1-7 (2.0±1.8) days after operation, and the patients recovered to normal life in 12 hours after the operation.Tenesmus (14/15), pain (5/15) and low fever (11/15) can alleviate without special treatment. All patients were follow up (19.0±2.6) months, bleeding symptoms were cured, there's no serious complications. Conclusion: The treatment of hemorrhoids by transcatheter superselective embolization of superior rectal artery is technically safe and feasible.

Predictor of massive bleeding following stent placement for malignant oesophageal stricture/fistulae: a multicentre study.

AIM: To evaluate retrospectively the incidence and predictors of massive bleeding after stent placement for malignant oesophageal stricture/fistulae. MATERIALS AND METHODS: This retrospective study comprised 519 patients with malignant oesophageal stricture/fistulae that were successfully treated with stent placement at three hospitals. The patients were divided into two groups based on the occurrence of massive bleeding. Univariate and multivariate analysis was performed to evaluate predictive factors of massive bleeding. RESULTS: Massive bleeding occurred in 54 of 519 patients 1-37 days following stent placement. All of the patients who developed massive bleeding died within 24 hours of the event. Univariate analysis showed massive bleeding was associated with the presence of a concomitant tracheal stent (p<0.001), the existence of concomitant oesophageal fistulae (p<0.001), and prior radiotherapy (p<0.001). Multivariate analysis exhibited that concomitant tracheal stent insertion (odds ratio [OR], 23.134; 95% confidence interval [CI], 9.523-56.199; p<0.001), the presence of oesophageal fistulae (OR, 3.724; 95% CI, 1.677-8.269; p=0.001), and prior radiotherapy (OR, 13.310; 95% CI, 5.464-32.421; p<0.001) were predictors of massive bleeding following stenting. CONCLUSIONS: The presence of oesophageal fistulae, prior radiotherapy, and concomitant tracheal stent are important factors contributing to bleeding after stenting.

Structure of glasses in the pseudobinary system Ga(2)Se(3)-GeSe(2): violation of chemical order and 8-N coordination rule.

Structure of glasses in the pseudobinary system Ga2Se3-GeSe2 with Ga2Se3 content ranging from 6.3 to 30 mol % is investigated using a combination of Raman and multinuclear ((71)Ga, (77)Se) solid state nuclear magnetic resonance (NMR) spectroscopy. The results indicate that the structure of these glasses consists primarily of a corner sharing network of (Ge/Ga)Se4 tetrahedra with some fraction of edge-sharing GeSe4 tetrahedra and of ethane-like (Se3)Ge-Ge(Se3) units, in which the Ga, Ge, and Se atoms adopt coordination numbers of 4, 4, and 2, respectively. As expected, the concentration of metal-metal bonds increases with addition of Ga2Se3 as the glass structure becomes too deficient in Se to satisfy the tetrahedral coordination of both Ga and Ge by Se atoms alone. These metal-metal bonds are mostly limited to Ge-Ge homopolar bonds, indicating a violation of chemical order. At relatively high degrees of Se-deficiency, however, spectroscopic evidence suggests the formation of triply coordinated Se atoms as an alternate mechanism to accommodate the tetrahedral coordination of Ga and Ge atoms. This observation indicates a violation of the 8-N coordination rule and is reminiscent of oxygen triclusters in isoelectronic Al2O3-SiO2 glasses. Compositional variation of physical properties such as density, molar volume, optical band gap, glass transition temperature, and fragility are shown to be consistent with the proposed structural model.

Stepwise regression analysis of the determinants of blood tacrolimus concentrations in Chinese patients with liver transplant.

Tacrolimus (FK506) is one of the immunosuppressive drugs used effectively to prevent allograft rejection after liver transplantation. Narrow therapeutic range and individual variance in pharmacokinetics make it difficult to establish a fixed dosage for all patients. Genetic polymorphism in drug metabolizing enzymes and in transporters may influence tacrolimus exposure. A stepwise regression analysis was used to analyze the relationship between blood concentrations of tacrolimus (54 blood samples at the day of 1 week, 2 week and one month after liver transplantation) and genetic & non-genetic factors in 18 Chinese liver transplant patients. The equation of multiple stepwise regression was: Y (tacrolimus' blood concentration) = 34.534 - 0.247 (age) - 0.510 (weight) + 1.688 (dose) + 6.876 (recipient's CYP3A5 genotype) - 3.097 (donor's CYP3A5 genotype), P < 0.01. The factors impacting patient's tacrolimus blood concentrations in a descending order are weight, recipient's CYP3A5 genotype, dose, age, donor's CYP3A5 genotype. Among those, patient's weight and recipient's CYP3A5 genotype could significantly impact the blood concentration of tacrolimus. The influence of recipient's CYP3A5 gene polymorphism is much more obvious than that of donor's. Neither donor's nor recipient's MDR1 genetic polymorphisms were correlated with the blood concentration of tacrolimus.

Treatment of malignant digestive tract obstruction by combined intraluminal stent installation and intra-arterial drug infusion.

AIM: To study the palliative treatment of malignant obstruction of digestive tract with placement of intraluminal stent combined with intra-arterial infusion of chemotherapeutic drugs. METHODS: A total of 281 cases of digestive tract malignant obstruction were given per oral (esophagus, stomach, duodenum and jejunum), per anal (colon and rectum) and percutaneous transhepatic (biliary) installation of metallic stent. Among them, 203 cases received drug infusion by cannulation of tumor supplying artery with Seldinger's technique. RESULTS: Altogether 350 stents were installed in 281 cases, obstructive symptoms were relieved or ameliorated after installation. Occurrence of restenotic obstruction was 8-43 weeks among those with intra-arterial drug infusion, which was later than 4-26 weeks in the group with only stent installation. The average survival time of the former group was 43 (3-105) weeks, which was significantly longer than 13 (3-24) weeks of the latter group. CONCLUSION: Intraluminal placement of stent combined with intra-arterial infusion chemotherapy is one of the effective palliative therapies for malignant obstruction of the digestive tract with symptomatic as well as etiological treatment.